Friend virus (FV) is a complex of two mouse retroviruses which induce rapid erythroleukemia in many strains of adult mice. This year our experiments have focussed on the influence of certain viral genes on two aspects of viral pathogenesis related to the helper virus component of the complex. Comparison of Friend MuLV versus Moloney MuLV as helpers for the defective SFFV component of the FV complex revealed that Moloney was far inferior to Friend as a helper virus in vivo. Subsequent experiments have used chimeric infectious viruses to determine which regions of Friend virus are required for high efficiency as a helper. The results indicate that two portions of the gag gene are involved in this effect, however the mechanism is still under investigation. Chimeric Friend/Moloney viruses from the above study were also used to determine the influence of different viral env genes on the interaction of FV complex with the immune system and in particular the major histocompatibility complex genes.Helper viruses with both the Moloney env and the AKV env are currently under experimentation. The role of mouse retroviral env gene variation in induction of neuropathogenesis is also being studied using the 98D strain of Friend MCF polytropic retrovirus. The results indicate that two different regions of the env gene can give a neurovirulent phenotype. These findings may have some similarities to brain disease induced by HIV in infected humans.